Changes in thrombolytic and inflammatory markers after initiation of indinavir- or amprenavir-based antiretroviral therapy

Erika M. Young, Robert V. Considine, Fred R. Sattler, Mark A. Deeg, Thomas A. Buchanan, Mikako Degawa-Yamauchi, Sudha Shankar, Hannah Edmondson-Melançon, Jaime Hernandez, Michael P. Dubé

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

HIV-infected subjects who have lipodystrophy and insulin resistance on prolonged antiretroviral therapy have elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens, markers of impaired thrombolysis that are associated with hyperinsulinemia and increased cardiovascular risk. We studied HIV-infected, protease inhibitor (PI)-naive adults treated with indinavir (n = 11) or amprenavir (n = 14) plus two nucleoside reverse transcriptase inhibitors enrolled in two independent prospective trials. Antiretroviral and immune responses were similar in both studies. Over 8 wk, indinavir was associated with decreased insulin sensitivity, whereas amprenavir was not. Levels of tPA antigen declined by approx 25% with both treatments (p < 0.05 for each); levels of PAI-1 antigen did not change. Levels of the inflammatory marker soluble tumor necrosis factor-alpha receptor II (sTNFr2) correlated positively with tPA antigen (r = 0.33, p = 0.02), and mean (SD) plasma concentrations of sTNFr also declined with treatment (4.44 1.11 ng/mL pretherapy, 3.75 1.21 posttherapy, p = 0.007). Short-term improvement in a marker of impaired thrombolysis and increased vascular risk can occur during PI-based antiretroviral therapy, perhaps as a consequence of improvement in HIV-related inflammation. This improvement occurred independent of development of insulin resistance, which occurred only with indinavir.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalCardiovascular Toxicology
Volume4
Issue number2
DOIs
StatePublished - Oct 14 2004

Keywords

  • Amprenavir
  • Antiretroviral therapy
  • Human immunodeficiency virus
  • Indinavir
  • Insulin resistance
  • Plasminogen activator inhibitor-1
  • Protease inhibitors
  • Tissue plasminogen activator
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine

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